Cytosolic dynein

The cytosolic dyneins bear many similarities to axonemal dynein. The protein isolated from C. elegans includes a heavy chain with a molecular mass of approximately 400 kD, as well as smaller peptides with molecular mass ranging from 53 kD to 74 kD. The protein possesses a microtubule-activated ATPase... 

Vallee, R.B., Wall, J.S., Paschal, B.M., Shpetner, H.S. (1988). Microtubule-associated protein 1C from brain is a two-headed, cytosolic dynein. Nature 332, 561-563. 

Microtubules with dynein arms or cytoskeletal microtubules to which cytosolic dynein or kinesin may attach dynein forms intertubule bridges during movement tubules are stable in cilia and flagella, but often labile in cytoplasm... 

Cytosolic dynein Kinetochores, centrosomes, cell cortex near spindle poles (-)... 

Cytosolic Dyneins Are (—) End-Directed Motor Proteins That Bind Cargo Through Dynactin... 

When the duplicated centrosomes have become aligned, formation of the spindle proceeds, driven by simultaneous events at centrosomes and chromosomes. As just discussed, the centrosome facilitates spindle formation by nucleating the assembly of the spindle microtubules. In addition, the (—) ends of microtubules are gathered and stabilized at the pole by dynein-dynactin working with the nuclear/mitotic apparatus protein. The role of dynein in spindle pole formation has been demonstrated by reconstitution studies in which bipolar spindles form in Xenopus egg extracts in the presence of centrosomes, microtubules, and sperm nuclei. The addition of antibodies against cytosolic dynein to this in vitro system releases and splays the spindle microtubules but leaves the cen-trosomal astral microtubules in position (Figure 20-35). 

The dynamic instability of spindle microtubules at the other end, the (+) end, is critical to their capture of chromosomes during late prophase as the nuclear membrane begins to break down. By quickly lengthening and shortening at its (-k) end, a dynamic microtubule probes into the chromosome-rich environment of the cell. Sometimes the (+) end of a microtubule directly contacts a kinetochore, scoring a bull s-eye. More commonly, a kinetochore contacts the side of a microtubule and then slides along the microtubule to the (+) end in a process that includes cytosolic dynein and mitotic kinesins... 

A EXPERIMENTAL FIGURE 20-35 Cytosolic dynein participates in the formation and stabilization of mitotic spindle poles. In vitro reconstituted spindles were stained with fluorescently-labeled polyclonal antibodies to tubulin (green) and dynein (red) and examined with a fluorescence microsope. In the control spindle left), cytosolic dynein is present at each tapered end, as well as at the equator. Addition of a dynein monoclonal antibody after the formation of the spindle right) disrupts dynein localization and causes the poles to splay. [From R. Fleald et at, 1997, J. Cell Biol. 138 615 courtesy of R. Fleald.]... 

A simple set of microtubule motor proteins—BimC, CENP-E, and cytosolic dynein—are conserved in all spindles. Additional motor proteins are present in more complex organisms. 

Mitotic spindle function relies heavily on microtubule motors. For each of the following motor proteins, predict the effect on spindle formation, function, or both of adding a drug that specifically inhibits only that motor Kin-C, BimC, cytosolic dynein, and CENP-E. 

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